Mass spectrometry (MS) is a central analytical technology that finds a large variety of applications in a broad range of fields, especially when coupled with a chromatographic separation technique such as gas chromatography (GC) or liquid chromatography (LC). While these chromatographic separation technologies of GC and LC provide significant merit in the separation of complex mixtures prior to their detection and identification by mass spectrometry, these separation methods also require long analysis times, typically in the order of 30-60 min. In addition, the long gas chromatography columns typically used can degrade thermally labile compounds in GC-MS analysis, while LC-MS suffers from poor mass spectral identification capability due to its use of electrospray or APCI for sample ionization rather than electron ionization, which is used with automated library based sample identification. As a result, several types of mass spectrometry probes have been developed in order to simplify and shorten the analysis time of essentially pure samples or samples in simple mixtures that do not require prior chromatographic separation. Most of these mass spectrometry (MS) probes are based on sample introduction via a miniature test tube (vial) that is introduced into the MS ion source through an airlock and bypass intermediate vacuum chamber, which has its own small vacuum pump in order to prevent air penetration into the MS ion source vacuum chamber. In addition, these probes have their own temperature controllers for the stabilization of sample vaporization rate (flux) at the ion source. As a result, these MS probes are expensive (typical price is in excess of $10,000) and although their use is much shorter in time than typical GC-MS or LC-MS analysis, it is not performed in real time and require about 5-10 min per analysis. Furthermore, due to the danger of leaks, standard MS probes cannot be operated or used by untrained personnel (such as students) due to the danger of excessive and detrimental leaks (detrimental to the vacuum pumps and ion source filaments) during the sample introduction procedure through the air lock chamber. Another significant downside to MS probes is the fact that the use of these probes is known to be involved with major and long lasting contamination of the MS ion sources due to small sample particles that fall inside the ion source. These contaminants reduce the probe sensitivity through the creation of a constant mass spectral background, lead to the necessity of periodic ion source cleaning, and complicate conversion of the system to GC-MS. A unique type of MS probe was developed in 1996 and later named ChromatoProbe (A. Amirav and A. Dagan, U.S. Pat. No. 5,686,656). This device is characterized by sample introduction in a small vial as in standard probes but the vials are introduced in a vial holder into a temperature controlled sealed GC injector for achieving a controlled sample vaporization rate, and the pressurized GC injector is connected to the MS ion source via a short capillary transfer line that acts as a flow restrictor. The ChromatoProbe solves some of the standard MS Probe problems but it still requires an approximately 5 minute analysis time due to the need to adjust the injector temperature to an optimal value and then cool it back for the next analysis (as well as sealing and pressure build-up time). In addition, the ChromatoProbe must employ a GC injector and hence requires the availability of a big GC near the MS for its application; additionally, with a current price of $3750, it is not inexpensive. Recently, desorption electrospray (DESI) and similar techniques have received significant attention as new methods that allow fast organic surface analysis without sample preparation through ambient (atmospheric) pressure ionization and ion transfer into the mass spectrometer. However, these techniques suffer from highly non-uniform response, are ineffective with several groups of compounds and do not share the extensive mass spectral information and library identification strength of electron ionization. Furthermore, they require expensive LC-MS instrumentation and cannot use the lower cost mass spectrometer of GC-MS instruments.
Thus, there is growing need for a simple MS probe device that will allow real time analysis with a cycle time of on the order of a few seconds, and that will be small, inexpensive, sensitive, and capable of fast self cleaning.
During the last 18 years, Amirav and coworkers have developed a new type of GC-MS which is based on the use of supersonic molecular beams (SMB) (also named Supersonic GC-MS). Supersonic GC-MS is based on GC and MS interface with SMB and on the electron ionization (EI) of vibrationally cold analytes in the SMB (cold EI) in a fly-through ion source. This ion source is inherently inert and further characterized by fast response and vacuum background filtration capability. The same ion source also offers a mode of classical EI. Cold EI, as a main mode, provides an enhanced ratio of molecular ion to fragment ions as well as effective library sample identification which is supplemented and complemented by a powerful isotope abundance analysis method and software. The range of low volatility and thermally labile compounds amenable to analysis is significantly increased due to the use of a contact-free fly-through ion source and the ability to lower sample elution temperatures through the unique use of high GC column carrier gas flow rates. Another important feature of the Supersonic GC-MS is its compatibility with very high column flow rates without any adverse effect on its sensitivity due to the availability of differential vacuum chamber for the supersonic nozzle. In fact, the Supersonic GC-MS was reported to be compatible with 240 ml/min column flow rate which is 240 times higher than prevailing in standard GC-MS. Thus, with the high flow rates of the Supersonic GC-MS, samples that are injected into volumes such as of the GC injector liners can be evacuated in less than a second. In contrast, in standard GC-MS the injection takes over a minute to evacuate ˜70% of the injector liner volume and about 10 minutes for full self cleaning. This difference is a major qualitative difference between the Supersonic GC-MS and standard GC-MS. However, it comes with a major penalty to the Supersonic GC-MS in the form of significant added complexity of added vacuum chamber, additional large vacuum pump, additional pneumatics, different ion source and its geometrical arrangement, added ion mirror and several other different aspects.
It is therefore a broad object of the present invention to provide an open probe method and device for sample introduction for mass spectrometry analysis.